There is an interest in determining the environmental and biological fate of various perfluoroalkyl compounds, including their partial decomposition products. There is as well a need for carbon labeling, which enables distinctive analytical monitoring for studying reaction kinetics and mechanisms. Perfluoroalkyl iodides (CnF(2n+1)—I) are important reactive intermediates in the chemistry of perfluoroalkyl compounds. The most widely used commercial route to prepare them consists of the telomerization of tetrafluoroethylene. This reaction generates the family of perfluoroalkyl iodides C2nF(4n+1)—I having an even number of carbon atoms, thus making them easily available for general synthetic use and further functionalization. For the studies described, 13C- and 14C-carbon labeled (or enriched) perfluoroalkyl or partially fluorinated alkyl derivatives are needed, wherein the labeled carbon atom is in the perfluoroalkyl group instead of within the hydrocarbon portion of the molecule. Having the labeled carbon in the perfluoroalkyl group would be advantageous because a perfluoroalkyl chain is chemically inert, and thus the carbon label would still remain a part of the partially fluorinated molecule even with the molecule's partial decomposition or conversion to other intermediates. Additionally, this stability would allow easy molecular recognition and detection in complex reaction mixtures or biological media.
Hereinafter the term “labeled” as applied to a carbon atom means that the concentration of 13C or 14C isotopic content has been significantly enriched. Commercial sources of labeled materials, such as barium carbonate-13C, are available with a 98 percent 13C atom enrichment. Among the 14C sources, barium carbonate-14C with higher than 50% (31.3 mCi/mmol) enrichment for 14C atom is used. The 14C isotope is radioactive, undergoing beta-decay with half-life of about 5700 years. Carbon-labeled compounds can be blended into the corresponding unlabelled (12C) compound for studies or analytical detection, a procedure known as “spiking”. Thus, the compounds with high (50-99%) isotope concentrations are preferred.
However, the synthesis of specifically labeled 13C- and 14C-carbon perfluoroalkyl compounds presents many challenges. Common fluorinated building blocks such as tetrafluoroethylene are not available in carbon-labeled form. Carbon-labeled tetrafluoroethylene is also not viewed as practical for the synthesis of individual n-perfluoroalkyl labeled materials, since it requires special safety handling measures not easily attainable in the laboratory. It is prone to polymerization, and its telomerization would lead to the mixture of homologs X(CF2CF2)nY rather than a single molecule. There are also considerable laboratory limitations to achieve perfluorination with powerful fluorination agents, such as elemental fluorine F2, and electrochemical fluorination in liquid HF. These procedures are typically used on the industrial scale to make various perfluoroalkyl building blocks and their derivatives. It is desirable to perform such labeled syntheses primarily on the laboratory scale using ordinary laboratory equipment. The synthesis of such carbon-labeled target organic molecules primarily employs labeled carbon sources (such as 13 or 14CO2, and Na13 or 14CN) that are widely commercially available, or labeled hydrocarbon intermediates (ethylene, acetic acid, etc.) that are more expensive and limited in availability.
A possible synthetic route for the preparation of 13C- and 14C-labeled perfluoroalkyl iodides is the Hunsdieker reaction of CnF(2n+1)—COOAg salts with iodine. An example of such methodology is the preparation of 1-14C-1-iodoperfluoropropane [Seleznev, V. G.; Skorobogatov, G. A., Slezar, O. N. “Photolysis of 1-14C-perfluoropropyl iodide with powerful light pulses” J. Org. Chem. USSR (Eng. Transl.), 12, 1976, 259]. However, such an approach requires the multi-stage synthesis of the labeled hydrocarbon acid precursors, which are further perfluorinated. It requires electrochemical fluorination expertise, special equipment, and handling of liquid hydrogen fluoride, all of which present safety issues. Additionally, perfluorination of relatively long n-alkyl chain hydrocarbon derivatives, using electrochemical fluorination or other means, can be incomplete or be accompanied by isomerization of the labeled alkyl chain. Such mixtures would not be acceptable for the end use, and pure compounds and their isomers would be very difficult to separate.
For the environmental, biological, analytical and other programs described above, it is desirable to have an easy and safe method to selectively prepare 13C- and 14C-labeled perfluoroalkyl iodides and their derivatives wherein the labeled carbon is within the perfluoroalkyl chain.
The present invention provides a selective process for the preparation of such perfluoroalkyl iodides and derivatives having a labeled carbon atom in a specific and terminal location of the perfluoroalkyl group. The process provides access to defined labeled compounds instead of a mixture of isomers.